The invention is applicable to apparatus in which a transducer modifies an applied electrical signal, in particular piezoelectric transducers, for example a quartz crystal microbalance system, where the transducer vibrates at a frequency at or close to its resonant frequency.
The transducer typically has an active surface on which a receptor group is immobilised. That group has a chemical affinity or reactivity towards the substance to be detected or analysed. The substance to be analysed is normally present in a fluid which is brought into contact with the active surface of crystal.
Physical, chemical and biochemical interactions between the receptor group on the surface and the substance cause a change in the mass attached to the surface (and in other physical properties of the active surface), and these affect the vibrational characteristics, in particular the resonant frequency, of the crystal. Analysis of these effects can be used to obtain qualitative and/or quantitative data on the substance.
In some types of known apparatus, the quartz crystal sensor is formed as part of flow cell which is connected to a sample delivery/removal system for passing a sample to be analysed through the cells so that the sample comes into contact with the crystal. The apparatus will include drive measurement circuitry connected to the crystal and operable to vibrate the crystal and to detect and/or measure the changes in the crystal's vibrational characteristics.
Replacement of the transducer is frequently necessary, particularly in the field of bio-sensors, if a number of different substances in fluid sample are to be analysed or if the receptor coating on the crystal cannot be used more than once.
In that connection it is known to provide the crystal and the flow cell in a single cartridge which may be readily inserted into and removed from apparatus providing the electrical circuitry and the sample delivery/removal system. An easily manufactured flow cell which is disposable, yet easily and robustly mountable into the measurement apparatus is therefore highly desirable.
U.S. Pat. No. 6,196,059 shows a cartridge formed from an injection moulded component having an annular rib to which the crystal is adhered. The rib spaces the crystal from an opposed face to define a flow cell, and the injection moulded component also includes recesses for contacts at a position spaced from the crystal. The contacts are connected to crystal by electrical wires, and provide a means of connection between the crystal and the appropriate drive/measurement circuitry.
Such a cartridge is of a relatively complex construction and is therefore relatively expensive, especially since the cartridge is to be used as a disposable unit. In addition, the minimum distance between the crystal and the underlying surface, and hence the volume of the flow cell, is limited by the rib, which provides a lower limit on the height of the flow cell. This can prevent the flow cell from achieving rapid immobilisation times, and this correspondingly limits the speed of response of the apparatus. Additionally the cartridge requires a manual electrical connection operation between the terminal of the transducer and the instrument, which is inconvenient in operation.
In the analysis of biomechanical interactions available volumes of analyte fluid are frequently limited so the volume of the flow cell should be small. It is also known that measurements of kinetic properties of analyte receptor interactions can be limited by the diffusion of analyte to the surface of the transducer. In order to minimise this transport limitation, and preferably overcome it, the dimension of the flow cell in the direction perpendicular to the transducer surface should be minimised.
The mounting of electromechanical piezo-electrical transducers such as quartz crystal oscillators in such a way that the mounted transducer is free of residual stress, and forms a reliable fluid tight seal is an important design objective of such cells. WO2128372 and WO0247246 propose various means intended to achieve stress free mounting, but in these cases there results a relatively complex multipart design for fabricating a leak tight structure, and further, as with U.S. Pat. No. 6,196,059 above this results in a situation where it is difficult to obtain a low volume of the flow cell.